In recent years, development of a drug eluting balloon (DEB) in which a balloon catheter is coated with drugs has been actively performed, and it has been reported to be effective in the treatment and prevention of restenosis. The balloon is coated by a coating film including drugs and additives, and when a blood vessel is dilated, the balloon presses against a blood vessel wall, and it delivers the drugs to target tissue.
In recent years, it has been found that a morphological form of the drugs coated on the balloon surface influences releasing property and tissue transferability of drugs from the balloon surface in a lesion affected area, and it is known that control of the crystal form or amorphous form of drugs is important.
International Publication No. WO2010/124098 and JP-T-2012-533338 disclose a method in which by using annealing by solvent vapor, the morphological form of drugs coated on a balloon surface is changed from the amorphous to the crystal form. JP-T-2012-533338 further discloses that the crystal form of paclitaxel obtained by annealing has a fan-like form and a rod-like form or a needle-like form, and the rod-like crystal form has a higher concentration of drugs in the target tissue compared to the fan-like form.
In addition, JP-T-2012-514510 discloses that paclitaxel in a crystalline hydrated form is coated, and the crystalline hydrated form has a preferable releasing property and tissue transferability of drugs in the lesion affected area compared to a non-hydrated form and the amorphous.
Thus, JP-T-2012-514510 discloses that the drug eluting balloon having a crystal form paclitaxel exhibits excellent tissue transferability of drugs; however, it does not describe the detailed morphological form of a crystal and an intravascular stenosis inhibitory effect.
In contrast, there is a concern that the drug eluting balloon having a crystal form paclitaxel exhibits strong toxicity with respect to target tissue in some cases. Therefore, in the recent development of the drug eluting balloon, it is required that the drug eluting balloon have both performance, that is, a high effect (intravascular stenosis inhibitory effect) of drugs and low toxicity. In PCT International Publication No. WO2010/124098, JP-T-2012-533338 and JP-T-2012-514510, the toxicity is not described at all, and a crystalline morphological form of a drug for obtaining performance in which the stenosis inhibitory effect is high and the toxicity is low is not yet clear.
Based on what has been described above, since it cannot be said that the drug eluting balloon having a coating layer in the related art sufficiently exhibits low toxicity and a high effect on a stenosis inhibition rate when treating a stenosis portion in a blood vessel, a medical instrument of which the toxicity is even lower and the stenosis inhibiting effect is high is desired.